Download Arterial Stiffness Is Associated with Orthostatic Hypotension in

Arterial Stiffness Is Associated with Orthostatic Hypotension in
Elderly Subjects with History of Falls
Jacques Boddaert, MD, w Hani Tamim, MD, Marc Verny, MD,w and Joël Belmin, MD
OBJECTIVES: To test the hypothesis that impaired hemodynamic orthostatic changes commonly observed in the
elderly may be related to age-related increase in arterial wall
stiffness.
DESIGN: Convenience sample of consecutive patients
admitted for falls.
SETTING: Acute- and intermediate-care geriatric ward of
a French hospital.
PARTICIPANTS: Fifty-seven elderly patients (46 women)
consecutively admitted to a geriatric ward with a history of
recent falls.
MEASUREMENTS: Orthostatic hypotension (OH) was
assessed using blood pressure measurements in the supine
position and 1, 2, and 3 minutes after standing. Arterial
wall stiffness was assessed using upper-limb and aortic
pulse-wave velocities, measured with an external pressure
transducer connected to a computer.
RESULTS: OH was present in 18 patients with a mean
age standard deviation of 85.4 7.6 (5 men, 13 women)
and absent in 39 patients aged 83.7 6.2 (6 men, 33
women). Upper-limb pulse-wave velocity was significantly
higher, by 16%, in patients with OH than those without
(9.91 vs 8.53 m/s; Po.02). Significant correlations were
found between upper-limb pulse-wave velocity and systolic
blood pressure changes after 1 minute of standing
(r 5 0.263, Po.05) and maximal diastolic blood pressure
change after standing (r 5 0.351, Po.01).
CONCLUSION: Upper-limb arterial wall stiffness was
significantly greater in elderly patients with OH than in
patients without OH and was significantly related to blood
pressure changes after standing. These results highlight the
possible role of age-related changes in the arterial tree in
the hemodynamic response to orthostatic challenges. J Am
Geriatr Soc 52:568–572, 2004.
Key words: elderly; orthostatic hypotension; arterial
stiffness
From the Service de Médecine Interne Gériatrique, Hôpital Charles Foix
et Université Paris 61, Ivry-sur-Seine, France; and wCentre de Gériatrie,
Hôpital Pitié-Salpétrière, Paris, France.
Address correspondence to Prof. Joël Belmin, Service de Médecine Interne
Gériatrique, Hôpital Charles Foix et Université Paris 613, 94 200
Ivry-sur-Seine, France. E-mail: [email protected]
JAGS 52:568–572, 2004
r 2004 by the American Geriatrics Society
O
rthostatic hypotension (OH) is a major health problem in the elderly and is extremely common in older
individuals. It affects 6% to 33% of community-dwelling
people aged 65 and older and much larger proportions of
elderly institutionalized patients.1–4 OH can cause dizziness
and falls and may lead to functional impairment, hospitalization, altered quality of life, and vital complications.5–9 It
is also considered to be a risk factor for stroke.10
The hemodynamic response to orthostatic challenge
involves many factors, grouped together in the baroreflex
arch. Orthostatic challenge is responsible for blood redistribution in the lower parts of the body and for decreases in
blood pressure (BP) and cardiac preload. In response, carotid
and aortic arterial wall receptors activate the baroreflex,
which reduces parasympathetic activity and increases sympathetic nervous system activity. Stimulation of the a-adrenergic
component leads to vasoconstriction and increased peripheral arterial resistance and stimulation of the b-adrenergic
component of increased heart rate and contractility.
The hemodynamic response to orthostatic challenge
involves several organs, which all play a significant part in
regulating BP. They include the arterial tree, heart, and
nervous system, particularly the autonomic nervous system.
The arterial tree plays a crucial part in this mechanism, first
because the detection of BP changes involves sensors
located in the arterial wall, and second because the
hemodynamic response mostly relies on vasomotion, which
depends on effectors also located in the arterial wall. Many
researchers have investigated the age-related changes in the
autonomic nervous system in an attempt to understand why
the hemodynamic response to orthostatic challenge is
altered in the elderly,11 but few have explored the role of
arterial aging. Because several defects in the arterial wall,
especially arterial stiffening, which reduces its elasticity and
contractility, characterize senescence,12,13 it was postulated
that age-related arterial stiffness might be involved in the
hemodynamic response to orthostatic challenge. In particular, it was hypothesized that pulse-wave velocity, a reliable
marker of arterial stiffness, might be correlated with the
magnitude of BP change during postural testing.
METHODS
Subjects
Consecutive patients admitted for falls to an acute- and
intermediate-care geriatric ward of a French hospital were
0002-8614/04/$15.00
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APRIL 2004–VOL. 52, NO. 4
considered for participation in the study. Patients were
eligible if they had a history of recent falls and were able to
transfer from bed to standing and remain upright. Moreover, exclusion criteria were unstable medical conditions,
including anemia, dehydration, heart failure, or infections,
and recent change in drug regimen. Fifty-seven elderly
patients comprising 11 men and 46 women were studied
(mean age standard deviation (SD) 5 84.2 6.7).
Orthostatic Tests
Blood pressure was measured in the nondominant arm
using an automatic oscillometric monitor (Dinamap,
Critikon model 1846 SX, GE Medical Systems, Fairfield,
CT) and a size-adapted arm cuff. Supine BP was measured
after patients had rested for 10 minutes or more in a quiet
environment in the presence of the physician, without
talking, moving, or smoking. Three successive measurements were made to ensure that resting supine BP was stable
and to accustom patients to the automatic device. The last
measurement was the one considered for the study. Upon
completion of these measurements, the patient was asked to
stand up, and BP was measured at 1, 2, and 3 minutes after
orthostatic challenge. According to the Consensus Committee of the American Autonomic Society and the
American Academy of Neurology,14 OH was defined as
patients who exhibited a drop of 20 mmHg or more in
systolic BP (SBP) or 10 mmHg or more in diastolic BP (DBP)
at any of the three standing BP measurements. The key
measure of this study, the hemodynamic response to an
orthostatic challenge, was determined by calculating the
changes in SBP and DBP from baseline (DSBP and DDBP,
respectively), at 1, 2, and 3 minutes after orthostatic
challenge. For example, a SBP increase of 40 mmHg at 2
minutes was expressed as DSBP-2 5 140 mmHg. Because
the largest drop in BP is believed to determine the largest
reduction in cerebral blood flow and symptoms, and
because kinetics of BP change during orthostatic challenge
varies between individuals, the largest changes from baseline in SBP and DBP (DSBP max and DDBP max) were
studied.
Pulse-Wave Velocity Measurements
With the contraction of the left ventricle, the ejection of
blood into the ascending aorta generates a pulse wave that
is propagated through the arterial tree. The measurement of
the pulse-wave velocity is a well-recognized way of
evaluating arterial distensibility: the stiffer the arterial wall,
the faster the pulse wave. Here, the pulse waves were
recorded using pressure-sensitive transducers, and pulsewave velocity was measured just before the orthostatic
challenge in supine resting conditions, using the Complior
device (Colson, Garges-les-Gonesse, France). Aortic pulsewave velocity was first measured by applying two external
pressure transducers to the carotid and femoral pulses. The
arterial pulse waves were recorded simultaneously and
processed by software specially designed to automatically
determine the interval between pulse waves (Colson). Pulsewave velocity was calculated as the ratio of the distance
between the transducers to the interval between two pulse
waves. The average for each patient was based on 10 pulsewave recordings.15 Upper-limb pulse-wave velocity was
ARTERIAL STIFFNESS AND ORTHOSTATIC HYPOTENSION
569
determined using the same methodology, except that a
transducer was placed on the brachial artery pulse at the
wrist instead of the femoral pulse.
Statistical Analysis
Univariate regression analyses were performed to evaluate
the relations between the studied parameters. Repeatedmeasures analysis of variance was used to compare mean
changes before and after orthostatic challenge in patients
with and without OH. All data are expressed as mean
SD. The significance level was set at Po.05.
RESULTS
Subjects
Baseline characteristics of the subjects are shown in Table 1.
Under resting conditions, SBP values were significantly
higher in patients with OH than in those without (148.6 21.3 vs 130.1 23.8 mmHg; Po.01). No significant differences were found between the two groups for DBP (74.8
8.3 vs 69.0 12.7 mmHg), pulse pressure (73.8 17.0
vs 63.8 20.7 mmHg), or heart rate (71.2 9.3 vs 72.8
11.1 beats/min).
BP and Heart Rate Responses to Orthostatic Challenge
BP responses during the orthostatic challenge are shown in
the Table 2. According the definition detailed in the
Table 1. Baseline Characteristics of Elderly Patients with
or without Orthostatic Hypotension (OH)
Characteristic
Age, mean standard
deviation
Men/women
Hypertension, n (%)
Ischemic heart
disease, n (%)
Atrial fibrillation,
n (%)
Heart failure,
n (%)
Stroke, n (%)
Diabetes mellitus,
n (%)
Alcohol, n (%)
Dementia, n (%)
Depression, n (%)
Nitrates, n (%)
Calcium channel blockers,
n (%)
Angiotensin converting
enzyme inhibitor, n (%)
Others antihypertensive
drugs, n (%)
Psychotropic
drugs, n (%)
Po.05.
Without OH
(n 5 39)
83.7 6.2
6/33
22 (56)
12 (31)
With OH
(n 5 18)
85.4 7.6
5/13
13 (72)
2 (11)
4 (10)
6 (33)
4 (10)
2 (11)
5 (13)
3 (8)
3 (17)
1 (6)
2 (5)
12 (31)
9 (23)
8 (21)
4 (10)
3 (17)
4 (22)
2 (11)
6 (33)
6 (33)
8 (21)
0 (0)
6 (15)
5 (28)
21 (54)
7 (39)
570
BODDAERT ET AL.
APRIL 2004–VOL. 52, NO. 4
Table 2. Hemodynamic Characteristics of Elderly Patients
with or without Orthostatic Hypotension (OH)
Without OH
(n 5 39)
Characteristic
Systolic blood pressure,
mmHg
Diastolic blood pressure,
mmHg
Pulse pressure, mmHg
Heart rate, bpm
Upper-limb pulse wave
velocity, m/s
Aortic pulse wave
velocity, m/s
DSBP-1, mmHg
DSBP-2, mmHg
DSBP-3, mmHg
DDBP-1, mmHg
DDBP-2, mmHg
DDBP-3, mmHg
DSBP max, mmHg
DDBP max, mmHg
With OH
(n 5 18)
Mean Standard
Deviation
130.1 23.8
148.6 21.3
69.0 12.7
74.8 8.3
63.8 20.7
72.9 11.1
8.53 1.85
73.8 17.0
71.3 9.3
9.91 1.72
13.63 2.45
8.8 13.7
15.9 14.7
16.4 14.4
6.2 8.7
5.7 8.4
6.7 9.0
7.0 12.9
2.1 5.9
14.86 3.04
20.5 13.3w
16.4 11.4w
15.3 9.2w
10.1 6.2w
2.7 7.4
6.1 8.3w
23.8 11.2w
11.2 6.2w
Po.05; w Po.0001 compared with elderly patients without OH.
DSBP 5 change in systolic blood pressure; DDBP 5 change in diastolic blood
pressure from supine to standing for 1 minute (DSBP-1, DDBP-1), 2 minutes
(DSBP-2, DDBP-2), and 3 minutes (DSBP-3, DDBP-3). DSBP max and DDBP max
are the maximal SBP and DBP changes from supine to standing.
Methods section,14 18 subjects had OH. A drop in SBP of
20 mmHg or more or a drop in DBP of 10 mmHg or more
was found in 17 of these patients after 1 minute standing, in
12 after 2 minutes standing, and in 11 after 3 minutes
standing.
Pulse-Wave Velocity
Upper-limb pulse-wave velocity was 16% higher in patients
with OH than in those without (9.91 vs 8.53 m/s, Po.02)
(Table 2). Similarly, aortic pulse-wave velocity was 9%
higher in patients with OH, but this difference was not
significant (14.86 vs 13.63 m/s) (Table 2). Upper-limb pulsewave velocity correlated with resting SBP (r 5 0.344, Po
.01, y 5 0.027x15.285), resting DBP (r 5 0.347, Po.01,
y 5 0.057x14.924), and resting pulse pressure (r 5 0.375,
Po.01, y 5 0.049x14.444). No significant relationship
was found between aortic pulse-wave velocity and baseline
blood pressure.
Correlates of Orthostatic BP Changes
There was no significant correlation between DSBP max
and baseline SBP, DBP, or pulse pressure, but DDBP max
correlated with resting SBP (r 5 0.346, Po.01, y 5 0.123x
14.755) and resting DBP (r 5 0.293, Po.05, y 5 0.218x
13.38).
Significant correlations were also found between upperlimb pulse-wave velocity and both DDBP max (r 5 0.351, P
JAGS
o.01, y 5 1.571x 12.238) and DSBP-1 (r 5 0.263, Po
.05, y 5 2.662x 23.3741) but not other standing parameters (Figure 1). Similarly, aortic pulse-wave velocity correlated with DDBP max (r 5 0.401, Po.01, y 5 1.335x
16.692) but not with other standing parameters.
DISCUSSION
The main new finding in this study was that upper-limb
pulse-wave velocity was significantly greater in elderly
patients with OH than in patients with a history of falls but
without OH. In addition, a significant correlation was
found between the hemodynamic response to orthostatic
challenge and upper-limb and aortic pulse-wave velocity,
which are recognized indicators of arterial stiffness. These
findings support the view that arterial stiffness plays an
important role in the hemodynamic response to orthostatic
challenge, especially in elderly patients with OH.
This conclusion is consistent with prior research. In the
Systolic Hypertension in the Elderly Program cohort of
4,736 healthy community-dwelling older persons aged 60
and older with isolated systolic hypertension, OH was
found to be highly prevalent and was associated with higher
mean SBP under resting conditions.3 This suggested a link
between OH and reduced arterial compliance, because
isolated systolic hypertension is known to be mainly due to
arterial wall stiffening and because patients with isolated
systolic hypertension were found to have significantly
decreased arterial compliance.16 One study subsequently
suggested that vascular and neural deficits contribute to the
age-related decline in cardiovagal baroreflex gain.17
Furthermore, in 47 healthy men aged 19 to 76, another
study found a significant univariate correlation between
cardiovagal baroreflex sensitivity and both age and carotid
artery compliance.18
The current study was able to detect only strong links
between the hemodynamic response to orthostatic challenge or OH and pulse-wave velocity. Because of the small
number of patients, the possibility cannot be excluded that
more-subtle associations might have been missed because of
insufficient statistical power. In addition, frail elderly
inpatients who presented with several comorbid conditions
and were not drug free were studied. An important
limitation of this observational study was that all factors
were not controlled. Thus, any no causal relationship can be
drawn from the results. There were significant differences
between the characteristics of the two groups. In particular,
baseline SBP was higher and atrial fibrillation and the use of
antihypertensive drugs were more common in the patients
with OH than in patients without. Moreover, one cannot
exclude that these factors or another unrecorded confounding factor might intervene in the pathophysiology of OH.
Several mechanisms might account for the links
between arterial stiffness and the hemodynamic response
to orthostatic challenge. The activation of carotid and
aortic baroreceptors is a first step in the baroreflex response
and generates sympathetic/parasympathetic regulation.
Because these baroreceptors are located inside the arterial
wall and are triggered by stretch, arterial stiffness may
interfere with their activation, thus explaining the decline in
baroreceptor sensitivity.11 In addition, because orthostatic
challenge generates sympathetic-dependent vasoconstriction,
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APRIL 2004–VOL. 52, NO. 4
ARTERIAL STIFFNESS AND ORTHOSTATIC HYPOTENSION
14
The hypothesis that arterial stiffening is a determinant
factor in the hemodynamic response to orthostatic challenge implies that it should be considered as a therapeutic
target. If so, interventions capable of reducing arterial
stiffness could be expected to improve the hemodynamic
response to orthostatic challenge and diminish the occurrence of OH. The benefit of a regular aerobic-endurance
exercise regimen was reported for central arterial compliance28 and for cardiovagal baroreflex sensitivity and
carotid artery compliance.18 Other types of interventions
might be capable of improving arterial compliance, but
their effect on the hemodynamic response to orthostatic
challenge is not known. In rats, aminoguanidine was found
to prevent the formation of advanced glycation endproducts involved in arterial stiffening with aging and to
lessen the age-related decrease in carotid distensibility.29
Similar results were subsequently found in humans, using
an advanced glycation end-product cross-link-breaker
regimen,30 but their effects on the hemodynamic response
to orthostatic challenge have not been reported.
The involvement of arterial stiffness in age-related
hemodynamic homeostatic changes is a relatively new and
interesting concept that may help improve understanding of
the hemodynamic response to orthostatic challenge and the
occurrence of OH in the elderly. In addition, interventions
might be capable of improving arterial compliance, but
their effects on hemodynamic response to orthostatic
challenge are not known.
6
8
10
12
14
Upper limb pulse wave velocity (m.sec-1)
ACKNOWLEDGMENTS
The authors thank Prof. Gabriel Gold (Geneva, Switzerland) for his help in the preparation of the manuscript.
A
Maximal orthostatic change in DBP
(mmHg)
30
20
10
0
-10
-20
4
6
8
10
12
B
SBP change at 1 min.
(mmHg)
40
20
0
-20
-40
4
571
Figure 1. Correlation between upper-limb pulse-wave velocity
and the maximal drop on diastolic blood pressure (DBP) (Panel
A) and systolic blood pressure (SBP) drop for 1 minute standing
(Panel B).
arterial stiffness might reduce the vasoconstricting potential
of the arterial wall. Nevertheless, this study was not
designed to elucidate the mechanisms involved in this
decline.
Age-related changes in the nervous system have been
implicated as the main factor responsible for the impaired
hemodynamic response to orthostatic challenge that occurs
with aging and for the frequent occurrence of OH in the
elderly. Many authors reported a decline in baroreceptor
sensitivity,11,19 a reduced sympathetic nervous system activation to orthostatic challenge, or a diminished vasomotor
response to sympathetic nervous system activation with
aging,20,21 but there is a large body of data supporting the
concept that the basal activity of the sympathetic nervous
system increases with aging,22–25 a paradox that has been
attributed to the uncoupling of beta-adrenergic receptors.26
Moreover, there is a recent report that indicates that the
vestibulosympathetic reflex declines with age and suggests
that this plays a role in OH in the elderly.27 Arterial
stiffening might also contribute to the age-related impairment of the hemodynamic response to orthostatic challenge
and to OH in the elderly and might constitute an additive
mechanism in relation to the changes in the autonomic
nervous system.
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